Lipid Matters

An occasional series of notes on publications or other items dealing with lipid science from a variety of contributors.

6th September 2024

High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases

It is well known that lipids play an important role in respiratory physiology (think surfactant). A recent study by Jia et al has added another lipid, oleic acid, in the replication of influenza virus and severity of disease (Jia et al). The investigators examined patients hospitalized with avian A(H7N9) influenza to identify early drivers of fatal disease. In a transcriptomics study they found that oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating the release of oleic acid from the oleyl-acyl-carrier protein, was strongly linked to fatal A(H7N9) disease. Interestingly, high OLAH levels were correlated with life-threatening seasonal influenza, COVID-19, respiratory syncytial virus (RSV), and multisystem inflammatory syndrome in children (MIS-C).  Using OLAH knockout (olah-/-) mice, a lethal dose of influenza virus led to survival and mild disease as well as reduced lung viral loads, tissue damage, infection-driven pulmonary cell infiltration, and inflammation.  The investigators further showed that the inhibition of lipid droplet formation led to reduced viral infection in macrophages and supplementation of oleic acid increased influenza virus infection in macrophages and inflammation.  The authors suggest these data provide mechanistic insights into how the expression of OLAH drives life-threatening respiratory disease.

Daniel M. Raben

The John Hopkins University School of Medicine, Baltimore, MD, USA


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